CSP #565 - Combination Angiotensin Receptor Blocker and Angiotensin Converting Enzyme Inhibitor for Treatment of Diabetic Nephropathy (VA NEPHRON-D Study)
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 1,448
- 试验地点
- 31
- 主要终点
- A Composite Endpoint of Reduction in Estimated GFR of 30ml/Min/1.73m*m in Individuals w/a Baseline Estimated GFR >= 60 ml/Min/1.73m*m, Reduction in Estimated GFR >50% in Individuals w/ Baseline Estimated GFR <60ml/Min/1.73m*m; ESRD or Death
研究概览
简要总结
Diabetes is the leading cause of end-stage renal disease (ESRD) in the United States. The overall rate of ESRD secondary to diabetes has risen 68% since 1992. Medications that block the renin angiotensin system have been shown to decrease the progression of diabetic nephropathy. The use of an angiotensin receptor blocker (ARB) has been shown to decrease the risk of progression of kidney disease in two studies of individuals with Type 2 diabetes and proteinuria. Despite the use of an ARB, the incidence of renal failure remained high in the treated group in both studies. The combination of an angiotensin converting enzyme inhibitor (ACEI) and ARB can lead to more complete blockade of the renin angiotensin system. In diabetic kidney disease, combination therapy has been shown to decrease proteinuria in short-term studies. Although there are encouraging results for improvement in proteinuria there are no data on progression of kidney disease for the use of combination of ACEI and ARB therapy in patients with diabetes. In addition, there could be an increased risk of serious hyperkalemia in individuals with diabetes who receive combination ACEI and ARB. The investigators therefore propose a randomized double blind multi-center clinical trial to assess the effect of combination of ACEI and ARB in patients with diabetes and proteinuria on progression of kidney disease.
详细描述
Primary Hypothesis:
To evaluate the combination of an angiotensin converting enzyme inhibitor (ACEI) with an angiotensin receptor blocker (ARB) vs. standard treatment with angiotensin receptor blocker on the progression of kidney disease in individuals with Type 2 diabetes and overt nephropathy.
The primary outcome is a composite endpoint of reduction in estimated GFR of 30 ml/min/1.73m*m in individuals with an estimated baseline GFR greater than or equal to 60 ml/min/1.73m*m; reduction in estimated GFR of greater than 50% in individuals with an estimated baseline GFR less than 60 mL/min/1.73m*m; progression to end-stage renal disease (defined as need for dialysis, renal transplant or an eGFR less than 15 ml/min/1.73m*m) or death.
Secondary outcome: a renal composite endpoint, defined as; reduction in estimated GFR of more than 50% (for individuals with a baseline estimated GFR less than 60 ml/min/1.73m*m); reduction in estimated GFR of more than 30 ml/min/1.73m*m (for individuals with a baseline estimated GFR greater than or equal to 60 ml/min/1.73m*m) or progression to end-stage renal disease (defined as need for dialysis, renal transplant or an eGFR of less than 15 ml/min/1.73m*m).
Tertiary outcomes are cardiovascular events (cardiovascular mortality, myocardial infarction, cerebrovascular accident, admission for heart failure), change in albuminuria at 12 months and decline in slope of kidney function.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Care Provider)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Type 2 diabetes
- •Albuminuria >300mg/gram creatinine
- •Stage 2 or 3 CKD (eGFR 30 to <90 mg/min/1.73m*2 )
- •Able to give informed consent
- •Telephone contact available
排除标准
- •History of intolerance to ACEI or ARB
- •Serum potassium level >5.5 meq/L
- •Receiving sodium polystyrene sulfonate (Kayexalate)
- •Pregnancy, breast feeding, planning to become pregnant or sexually active and not using birth control
- •Renal transplant recipient
- •Suspected non-diabetic kidney disease
- •Inability to discontinue current use of ACEI/ARB combination
- •Current use of Lithium
- •Severe (end-stage) comorbid disease
- •Estimated glomerular filtration rate (GFR) <30 or >=90 ml/min/1.73m*m
- •HbA1c >10.5%
- •Patient refusal
- •Participation in a concurrent interventional study
- •Blood pressure >180/95
- •Unwilling to stop any proscribed medications after enrollment
研究组 & 干预措施
Combination of ARB and ACEI
Combination of an angiotensin converting enzyme inhibitor (ACEI) with an angiotensin receptor blocker (ARB)
干预措施: losartan (Drug)
Combination of ARB and ACEI
Combination of an angiotensin converting enzyme inhibitor (ACEI) with an angiotensin receptor blocker (ARB)
干预措施: lisinopril (Drug)
Monotherapy ARB
Mono therapy arm. Standard treatment with angiotensin receptor blocker (ARB)
干预措施: losartan (Drug)
结局指标
主要结局
A Composite Endpoint of Reduction in Estimated GFR of 30ml/Min/1.73m*m in Individuals w/a Baseline Estimated GFR >= 60 ml/Min/1.73m*m, Reduction in Estimated GFR >50% in Individuals w/ Baseline Estimated GFR <60ml/Min/1.73m*m; ESRD or Death
时间窗: From enrollemnt to time of first primary event, up to 4.5 years
Time to the first event of reduction in estimated GFR of 30ml/min/1.73m\*m in individuals w/a baseline estimated GFR \>= 60 ml/min/1.73m\*m, reduction in estimated GFR \>50% in individuals w/ baseline estimated GFR \<60ml/min/1.73m\*m; ESRD or death.
次要结局
- A Renal Composite Endpoint, Defined as; Reduction in Estimated GFR of >50% (for Individuals With Baseline GFR <60) or Reduction in GFR of >30 (for Individuals With Baseline GFR >= GFR 60) or ESRD.(From enrollment to time of first event, up to 4.5 years)